| 1. |
- Münch, Andreas
(författare)
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Collagenous colitis : The influence of inflammation and bile acids on intestinal barrier function
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Collagenous colitis (CC) is a diarrheal disorder with an incidence rate of 5-6/100000 inhabitants, affecting mainly middle-aged women. The diagnosis is made by histology of the colonic mucosa. Classical findings are a thickened subepithelial collagenous layer and chronic inflammation in the lamina propria. In inflammatory bowel disease (IBD) the mucosal barrier function is important in pathogenesis. The main purpose of the thesis was therefore to describe the barrier function in CC. The cause of CC is uncertain but the condition seems to be associated with bile acid malabsorption. Increased faecal bile acids are known to induce diarrhea. In functional studies the influence of bile acids on mucosal permeability in biopsies of healthy human individuals and in patients with CC was investigated.Methods and patients: In the first paper a single patient with intractable CC was examined before surgery, with loop-ileostomy and after bowel reconstruction. For the other studies a total of 25 patients with CC were included (20 women, 5 men, mean age 66 years). There were three groups (14 patients in clinical remission without medical treatment, 11 with active disease, and 8 of these again after 6 weeks of budesonide treatment); 17 individuals with normal histology served as controls. Endoscopic biopsies from the sigmoid colon were mounted in modified Ussing chambers and assessed for short-circuit current (Isc), transepithelial resistance (TER), and transmucosal passage of chemically killed E. coli K12 after addition of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA). The biopsies were further investigated with confocal microscopy to assess bacterial transepithelial passage.Results: Para- and transcellular permeability was increased in active CC, but normalized with histological improvement due to faecal stream diversion. After bowel reconstruction, permeability to CrEDTA and HRP increased again.In CC, bacterial uptake in colonic biopsies was significantly higher in all groups than in controls. Despite significant alleviation of symptoms, budesonide did not normalize the increased bacterial passage. Histology was unchanged after 6 weeks of budesonide treatment. DCA augmented mucosal permeability to CrEDTA in a dose-dependent manner and even such a low dose as 100 μmol/l DCA increased bacterial uptake significantly. The combination of bile acids and E.coli K12 had additive effects on TER.100 μmol/l CDCA and DCA increased bacterial uptake in biopsies of CC patients in remission 4-fold, but had no additive effect on biopsies from patients with active disease. Furthermore, patients in clinical remission on budesonide treatment showed no bile acidinduced effects on E.coli K12 passage.Conclusion: Collagenous colitis presents with increased para/transcellular permeability and bacterial uptake, irrespective of disease activity or budesonide treatment, signifying an underlying mucosal barrier defect. Faecal stream diversion can normalize the barrier dysfunction, but budesonide does not, despite its beneficial clinical effects which alleviate diarrhea or bowel symptoms. Bile acids in physiological concentrations have the potential to augment bacterial uptake, especially in mucosa from CC patients in remission. Budesonide treatment appears to counteract the bile acid induced mucosal impairment. These detrimental effects of bile acids on mucosal barrier function might facilitate initiation and perpetuation of mucosal inflammation in CC.
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| 2. |
- Ström, Linda, 1985, et al.
(författare)
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Catalytically Active Pd–Ag Alloy Nanoparticles Synthesized in Microemulsion Template
- 2018
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 34:33, s. 9754-9761
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the possibility to form catalytically active bimetallic Pd–Ag nanoparticles synthesized in the water pools of a reversed microemulsion using methanol, a more environmental- and user-friendly reductant compared to hydrazine or sodium borohydride, which are commonly used for this type of synthesis. The nanoparticles were characterized with regards to crystallinity and size by X-ray diffraction and transmission electron microscopy. CO chemisorption and oxidation followed by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was used for investigating the elemental composition of the surface and catalytic activity, respectively. Moreover, the structural composition of the bimetallic particles was determined by scanning transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy. The particles were shown to be crystalline nanoalloys of around 5–12 nm. CO adsorption followed by in situ DRIFTS suggests that the particle surfaces are composed of the same Pd–Ag ratios as the entire particles, regardless of elemental ratio (i.e., no core–shell structures can be detected). This is also shown by numerical simulations using a Monte Carlo based model. Furthermore, CO oxidation confirms that the synthesized particles are catalytically active.
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| 3. |
- Ström, Linda, 1985, et al.
(författare)
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Quantification of urea-spray non-uniformity effects on the H2-assisted NO reduction and NH3 slip over an Ag/Al2O3 catalyst
- 2015
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 75, s. 2317-2322
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Konferensbidrag (refereegranskat)abstract
- Selective catalytic reduction of nitrogen oxides (NOx) with ammonia (NH3-SCR) is an efficient technology for lean NOx removal in automotive applications. In the current work, a kinetic model for hydrogen-assisted NH3-SCR over a silver-alumina (Ag/Al2O3) monolith catalyst is adapted to the corresponding experimental results. The degree of non-uniformity in the NH3 dose to individual catalyst channels during operation of a urea-SCR system is also investigated and the NH3 dose probability distribution functions are derived. The effects of NH3 non-uniformity on the NO conversion and NH3 slip are studied over an otherwise optimal Ag/Al2O3 system. Above the stoichiometric point, the NH3 slip is shown to increase almost linearly with increasing NH3 dosage. Channels that receive significantly lower NH3 dose than the stoichiometric one exhibit low NO conversion, whereas there is no discernable increase in the NO conversion above an NH3 dose four times the average. These results highlight the importance of the interaction between the design of the NH3 dosing system and the performance of the catalytic system.
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| 4. |
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| 5. |
- Agebratt, Christian, et al.
(författare)
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A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1, s. e0147149-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.ObjectivesTo study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.MethodsThirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.ResultsWeight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.ConclusionsAlthough BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.
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| 6. |
- Bednarska, Olga, et al.
(författare)
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Intraepithelial lymphocyte distribution differs between the bulb and the second part of duodenum
- 2013
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Ingår i: BMC Gastroenterology. - : BioMed Central. - 1471-230X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEvaluation of intraepithelial duodenal lymphocytosis (IDL) is important in celiac disease (CD). There is no established cut-off value for increased number of IELs in the bulb.We therefore investigated the relation between IEL counts in the bulb and duodenal specimens in non-celiac subjects.MethodsThe number of CD3+ IELs was determined in specimens from the second part of the duodenum and from the bulb in 34 non-celiac subjects. The numbers of IELs in the villus tip and sides were counted and the quotient tip/side was calculated. HLA DQ2/DQ8 and serum antibodies against transglutaminase were analysed.ResultsThe mean number of IELs per 100 enterocytes (95% CI) in specimens was 14.7 (11.8-17.6) in the bulb, and 21.2 (17.0-25.5) in the second part of the duodenum (p<0.01). There was no difference in IEL count or distribution comparing patients carrying or lacking HLA DQ2/DQ8.ConclusionsIEL count in non-celiac, HLA DQ2/DQ8 positive or negative patients is significantly lower in the bulb than in the second part of the duodenum. These findings implicate that the site of biopsy should be taken into account when considering duodenal lymphocytosis.
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| 7. |
- Bednarska, Olga, 1973-
(författare)
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Peripheral and Central Mechanisms in Irritable Bowel Syndrome : in search of links
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Irritable bowel syndrome (IBS) is a chronic visceral pain disorder with female predominance, characterized by recurrent abdominal pain and disturbed bowel habits in the absence of an identifiable organic cause. This prevalent and debilitating disease, which accounts for a substantial economic and individual burden, lacks exact diagnostic tools and effective treatment, since its pathophysiology remains uncertain. The bidirectional and multilayered brain-gut axis is a well-established disease model, however, the interactions between central and peripheral mechanisms along the brain-gut axis remain incompletely understood. One of the welldescribed triggering factors, yet accounting for only a fraction of IBS prevalence, is bacterial gastroenteritis that affects mucosal barrier function. Altered gut microbiota composition as well as disturbed intestinal mucosal barrier function and its neuroimmune regulation have been reported in IBS, however, the impact of live bacteria, neither commensal nor pathogenic, on intestinal barrier has not been studied yet. Furthermore, abnormal central processing of visceral sensations and psychological factors such as maladaptive coping have previously been suggested as centrally-mediated pathophysiological mechanisms of importance in IBS. Brain imaging studies have demonstrated an imbalance in descending pain modulatory networks and alterations in brain regions associated with interoceptive awareness and pain processing and modulation, particularly in anterior insula (aINS), although biochemical changes putatively underlying these central alterations remain poorly understood. Most importantly, however, possible associations between these documented changes on central and peripheral levels, which may as complex interactions contribute to disease onset and chronification of symptoms, are widely unknown.This thesis aimed to investigate the peripheral and central mechanisms in women with IBS compared to female healthy controls (HC) and to explore possible mutual associations between these mechanisms.In Paper I, we studied paracellular permeability and passage of live bacteria, both commensal and pathogenic through colonic biopsies mounted in Ussing chambers. We explored the regulation of the mucosal barrier function by mast cells and the neuropeptide vasoactive intestinal polypeptide (VIP) as well as a correlation between mucosal permeability and gastrointestinal and psychological symptoms. We observed increased paracellular permeability and the passage of commensal and pathogenic live bacteria in patients with IBS compared with HC, which was diminished by blocking the VIP receptors as well as after stabilizing mast cells in both groups. Moreover, higher paracellular permeability was associated with less somatic and psychological symptoms in patients.In Paper II, we aimed to determine the association between colonic mucosa paracellular permeability and structural and resting state functional brain connectivity. We demonstrated different patterns of associations between mucosa permeability and functional and structural brain connectivity in IBS patients compared to HC. Specifically, lower paracellular permeability in IBS, similar to the levels detected in HC, was associated with more severe IBS symptoms and increased functional and structural connectivity between intrinsic brain resting state network and descending pain modulation brain regions. Our findings further suggested that this association between mucosa permeability and functional brain connectivity was mainly mediated by coping strategies.In Paper III, we investigated putative alterations in excitatory and inhibitory neurotransmission of aINS, as the brain’s key node of the salience network crucially involved in cognitive control, in IBS patients relative to HC and addressed possible connections with both symptoms and psychological factors. We found decreased concentrations of the excitatory neurotransmitter Glx in bilateral aINS in IBS patients compared to HC, while inhibitory neurotransmitter GABA+ levels were comparable. Further, we demonstrated hemisphere-specific associations between abdominal pain, coping and aINS excitatory neurotransmitter concentration.In conclusion, this thesis broadens the knowledge on peripheral and central mechanisms in IBS and presents novel findings that bring together the ends of brain-gut axis. Our results depict association between mucosal permeability, IBS symptoms and functional and structural connectivity engaging brain regions involved in emotion and pain modulation as well as underlying neurotransmitter alterations.
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| 8. |
- Bednarska, Olga, et al.
(författare)
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Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome
- 2017
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 153:4, s. 948-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND amp; AIMS: Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study the passage of live bacteria through the colonic epithelium, and determine the role of mast cells (MCs) and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. METHODS: Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or MCs. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of MCs and MCs that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy. RESULTS: In colon biopsies from patients with IBS, larger numbers of E coli HS and S typhimurium passed through the epithelium than in biopsies from controls (P amp;lt;.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits MCs. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of MCs, and a higher percentage of MCs that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. CONCLUSIONS: We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria compared with controls. The mechanisms of increased translocation include MCs and VIP.
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| 9. |
- Bernin, Diana, 1979, et al.
(författare)
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Microstructure of polymer hydrogels studied by pulsed field gradient NMR diffusion and TEM methods
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:12, s. 5711-5716
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Tidskriftsartikel (refereegranskat)abstract
- The microstructure of various alginate gels have been studied by pulsed field gradient NMR (PFG NMR) and transmission electron microscopy (TEM). The reduced diffusivity of dendrimer diffusion within the gels has been obtained from PFG NMR diffusion experiments. The polymer strand radius, an important microstructural property, has been extracted from various diffusion models. The results agree well with the polymer strand radii obtained from image analysis of the corresponding TEM micrographs.
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| 10. |
- Daferera, Niki, et al.
(författare)
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Fecal stream diversion and mucosal cytokine levels in collagenous colitis : A case report
- 2015
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Ingår i: World Journal of Gastroenterology. - Pleasanton, USA : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 21:19, s. 6065-6071
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Tidskriftsartikel (refereegranskat)abstract
- In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.
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